Human papilloma virus (HPV) presence in primary tumors of the lacrimal sac: a case series and review of the literature.

Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.

Paediatric non-infectious granulomatous uveitis: a retrospective cohort study.

INTRODUCTION: Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging. OBJECTIVES: To evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis. METHODS: Retrospective chart review of non-infectious PGU occurring in children before the age of 16 years recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023. RESULTS: We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with juvenile idiopathic arthritis, and one with Vogt-Koyanagi-Harada disease. Median age at diagnosis was 9.8 years (range 7.2-12.5). The sex-ratio M/F was 0.52. The most common features of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%) particularly in cases of panuveitis. The most commonly used treatments were systemic corticosteroids (72%) and methotrexate (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years. CONCLUSION: We report the largest cohort of PGU. PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.

Ocular surface toxicities associated with modern anticancer therapies.

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision. While these complications remain rare, they are probably underreported. It is likely that both oncologists and ophthalmologists will come across MATs-associated ocular surface-adverse events in their practices, owing to the increasing number of patients being treated with MATs. Rapid identification of ocular surface-adverse events is crucial, as early intervention can manage these conditions to avoid vision loss and reduce negative impacts on quality of life. We discuss characteristics of ocular surface pathologies attributed to MATs, describe the suspected underlying pathophysiological mechanisms, and outline the main lines of treatment.

IS CATARACT SURGERY SAFE IN PATIENTS WITH STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS?

PURPOSE: To assess the retinal modifications after cataract surgery in a patient presenting with stellate nonhereditary idiopathic foveomacular retinoschisis. METHODS: Retrospective analysis of the evolution of retinal status in a 64-year-old patient with unilateral stellate nonhereditary idiopathic foveomacular retinoschisis who underwent cataract surgery in the affected eye. RESULTS: Visual acuity improved after surgery, reaching back the level described by the patient before the cataract onset, whereas fundus retinographies and optical coherence tomographies were stable at one month after surgery, compared with the preoperative images. DISCUSSION: This first case-report of the evolution of stellate nonhereditary idiopathic foveomacular retinoschisis after cataract surgery suggests that this retinal condition is not modified by the surgical procedure, which however needs to confirmed by larger cohorts.

Specific postoperative complications of vitrectomy in hereditary transthyretin amyloidosis.

INTRODUCTION: Vitrectomy may improve visual acuity of hereditary transthyretin amyloidosis (ATTRv) patients presenting with vitreous opacities but is associated with severe complications. The objective of this study is to report visual outcomes, early and late complications of a series of ATTRv patients who underwent vitrectomy in the French ATTRv reference center. METHODS: This retrospective, single-center study, included all ATTRv patients who underwent vitrectomy between 2002 and 2017. Data were collected on pre and postoperative best corrected visual acuity (BCVA) and early and late postoperative complications. RESULTS: A total of 21 eyes from 15 patients were included. The mean postoperative follow-up was 40 ± 20 months (6-160 months). BCVA increased from 0.7 ± 0.4 LogMAR preoperatively to 0.3 ± 0.4 LogMAR (p = 0.003) at last postoperative visit. During follow-up, all initially glaucomatous eyes worsened, with three eyes (37%) requiring filtering surgery and two eyes (25%) had further vision loss. Among non-glaucomatous patients, four eyes (31%) developed glaucoma with two requiring trabeculectomy and one eye (8%) had further vision loss. Three eyes (three patients) presented with complications of amyloid angiopathy. Three eyes (three patients) experienced recurrence of vitreous deposits requiring surgical revision. CONCLUSION: Due to the potential complications, vitrectomy in ATTRv requires specific perioperative management and life-long postoperative monitoring.

Assessment of the duration of surgery and patient turnover after the incorporation of a standardized intracameral combination of mydriatics and anesthetics for cataract surgery.

PURPOSE: To evaluate changes in clinical outcomes, duration, and workflow of cataract surgery, before and after the introduction of a commercially available intracameral combination of 2 mydriatics (phenylephrine, tropicamide) and 1 anesthetic (lidocaine) (ICMA). SETTING: Service d'Ophtalmologie, Hôpital Bicêtre, Université Paris Sud., Le Kremlin-Bicêtre, France. DESIGN: Retrospective chart review. METHODS: Three series of patients who underwent cataract surgery were grouped according to when they had surgery: just before ICMA was approved (early 2016, Series I); just after implementation of ICMA as the standard procedure for surgery (late 2016, Series II); and 21 months after using ICMA routinely for surgery (2018, Series III). Data were collected on patient turnover during the day of surgery and surgical outcomes. RESULTS: The study population comprised of 51, 47, and 51 patients in Series I, II, and III respectively. There were no statistical differences between series in the mean change in corrected distance visual acuity from preoperatively to 1 month postoperatively and in complications (P > .05, all comparisons). The mean duration of surgery was significantly shorter in Series III and II, compared with Series I (13.18 ± 4.05 and 13.62 ± 5.26 vs 15.82 ± 6.01 minutes; P = .023 and P = .041, respectively). The mean patient rotation was statistically significantly shorter in Series III compared with Series I (41.50 ± 8.31 vs 47.79 ± 14.66 minutes, respectively; P = .028). CONCLUSIONS: Implementing ICMA as a routine procedure in cataract surgery resulted in similar vision and safety outcomes than the usual topical eyedrop regimen, while significantly reducing the total surgery and rotation times. Hence, patient turnover during the surgical session was optimized while maintaining safety and efficacy of the procedure.

The 2016-2019 ImmunoTOX assessment board report of collaborative management of immune-related adverse events, an observational clinical study.

PURPOSE: We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ specialists that adopts a real-life, case-by-case approach in the management of patients with immune-related adverse events (irAEs). EXPERIMENTAL DESIGN: The ImmunoTOX assessment board was set up in 2016 at Gustave Roussy in France. It meets every 2 weeks to discuss the case-by-case management of patients presenting with irAEs. Here, we describe the ImmunoTOX board's activities between 2016 and 2019. RESULTS: Over study period, 398 requests (concerning 356 patients) were submitted to the ImmunoTOX board. Most of the requests concerned the putative causal link between immunotherapy and the irAE (n = 148, 37%), followed by possible retreatment after temporary withdrawal because of an adverse event (n = 109, 27%), the clinical management of complex situations (n = 100, 25%) and the initiation of immunotherapy in patients with pre-existing comorbidities (n = 41, 10%). The ImmunoTOX board discerned 273 irAEs. The five organ systems most frequently involved by irAEs were lung (n = 58, 21%), gastrointestinal tract (n = 36, 13%), liver or biliary tract (n = 33, 12%), musculoskeletal system (n = 27, 10%), and nervous system (n = 23, 8%). The time to occurrence was shorter for severe irAEs (grade III and VI) than for mild irAEs (grades I and II), with medians of 47 and 91 days, respectively (p = 0.0216). CONCLUSION: The main medical needs in the management of irAEs involved the lung organ. Severe irAEs were expected to occur earlier than mild irAEs. This real-life study can help to better estimate medical needs and therefore help to assess the management of irAEs.

Conjunctival lymphangiectasia as a biomarker of severe systemic disease in Ser77Tyr hereditary transthyretin amyloidosis.

AIMS: To investigate the relationship between the ophthalmic and systemic phenotypes in patients with hereditary transthyretin amyloidosis with the S77Y mutation (ATTRS77Y). METHODS: In this cross-sectional study, patients with genetically confirmed ATTRS77Y amyloidosis were enrolled. All patients underwent complete neurological examination, including staging with the Neuropathy Impairment Score (NIS), Polyneuropathy Disability (PND) score; complete cardiological evaluation, including echocardiography, cardiac MRI and/or cardiac scintigraphy and complete ophthalmic evaluation, including slit lamp examination and fundus examination. Ocular ancillary tests (fluorescein and indocyanine green angiography, and anterior segment optical coherence tomography) were performed in cases with abnormal findings. The Kruskal-Wallis test was used for quantitative outcomes and Fisher's exact test for qualitative outcomes. Statistical significance was indicated by p<0.05 (two tailed). RESULTS: The study sample was composed of 24 ATTRS77Y patients. The mean patient age was 58.4±12.4 years. None of the patients presented with amyloid deposits in the anterior chamber, secondary glaucoma or vitreous amyloidosis. Retinal angiopathy was observed in four patients, complicated with retinal ischaemia in one patient. Conjunctival lymphangiectasia (CL) was detected in 13 patients (54%), associated with perilymphatic amyloid deposits. The presence of CL was statistically associated with more severe neurological disease (NIS=43.3±31.9 vs 18.9±20.4; PND=2.6±1.0 vs 1.4±0.7 in patients with and without CL, respectively; both p<0.05) and amyloid cardiomyopathy (p=0.002). CONCLUSION: In ATTRS77Y patients, CL is common and could serve as a potential biomarker for severe systemic disease. There were neither anterior chamber deposits, secondary glaucoma nor vitreous deposits in ATTRS77Y patients.

Prevalence and Clinical Patterns of Ocular Complications Associated With Anti-PD-1/PD-L1 Anticancer Immunotherapy.

PURPOSE: Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay of metastatic cancer treatment. Patients receiving these treatments may develop immune-related adverse events (irAEs). This study aimed to estimate the prevalence and describe the clinical patterns of moderate-to-severe ocular irAEs-associated with anti-PD-(L)1 treatment. DESIGN: Prospective case series. METHODS: This study included patients recruited via (1) a single-center prospective cohort and (2) a national pharmacovigilance registry between June 2014 and March 2018, and focused on patients with moderate-to-severe ocular irAEs following anti-PD-(L)1. All patients underwent a comprehensive ophthalmologic assessment. The main outcome measure was the prevalence of moderate-to-severe ocular irAEs. RESULTS: Of a total of 745 patients included in the prospective cohort, 3 developed moderate-to-severe ocular irAEs, providing a prevalence of 0.4% and an incidence of 0.7 per 1000 patient-months of treatment. An additional 5 cases of moderate-to-severe ocular irAEs were reported through the national registry. From these 8 patients, 5 presented with intraocular inflammation, 2 with ocular surface disease, and 1 with orbital myopathy. Five patients (62.5%) experienced additional extraophthalmologic irAEs. Ocular irAEs led to permanent discontinuation of anti-PD-(L)1 in 4 patients. Treatment by local and/or systemic corticosteroids allowed resolution or control of the ocular symptoms in 7 of 8 patients. CONCLUSION: Although uncommon, anti-PD-(L)1-associated ocular complications may be sight-threatening and lead to discontinuation of anti-PD-(L)1 treatments. Patients complaining of eye problems while receiving ICI treatment should immediately be seen by an ophthalmologist.

Angiographic Signatures of the Predominant Form of Familial Transthyretin Amyloidosis (Val30Met Mutation).

PURPOSE: To describe abnormalities in choroidal and retinal vasculature associated with Val30Met familial transthyretin amyloidosis (V30M-FTA) using fluorescein and indocyanine green (ICG) angiography. DESIGN: Prospective, cross-sectional study. METHODS: This study was conducted at the French National Reference Center for FTA. We included 18 consecutive genetically confirmed V30M-FTA patients (36 eyes) who underwent complete neurologic examination, including staging with polyneuropathy disability (PND) score, and complete ophthalmic evaluation, including staging of intraocular amyloid deposits and fluorescein and ICG angiograms (ICG-A). The grading of choroidal and retinal angiopathy, and their association with neurologic functional impairment, were the main outcome measures. RESULTS: Eleven men and 7 women, mean age 61.6 ± 12.1 years, were included. Retinal amyloid angiopathy (RAA) was detected in 24 eyes (92%) of 13 patients, with microaneurysms, retinal hemorrhages, and retinal ischemia of variable extent. Three patients (5 eyes) had neovascular glaucoma and 2 (2 eyes) had preretinal neovascularization. ICG-A indicated choroidal amyloid angiopathy (CAA) in all patients, with 3 distinct patterns-diffuse (9/18 patients), focal (5/18 patients), or punctiform (4/18 patients)-based on the extent of late hypercyanescence along the choroidal arteries. PND scores were significantly higher in patients with diffuse CAA (firework pattern) compared to those with limited CAA (focal and punctiform patterns) (2.89 vs 1.78, P = .045). CONCLUSION: RAA is a frequent and severe complication of V30M-FTA that may lead to anterior and posterior segment neovascularization. CAA was detected in all patients, with a late hypercyanescent delineation of the choroidal arterial vasculature, which was more extensive with increased disease severity.

Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy.

IMPORTANCE: Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN. OBJECTIVE: To determine the correlation of SFN with IVCM in patients with TTR-FAP. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR-FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM. MAIN OUTCOMES AND MEASURES: Correlation of corneal nerve fiber length (CNFL) with the severity of SFN. RESULTS: Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P < .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P < .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P < .001). CONCLUSIONS AND RELEVANCE: In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR-FAP.

Biometry and intraocular lens power calculation results with a new optical biometry device: comparison with the gold standard.

PURPOSE: To evaluate the agreement in axial length (AL), keratometry (K), anterior chamber depth (ACD) measurements; intraocular lens (IOL) power calculations; and predictability using a new partial coherence interferometry (PCI) optical biometer (AL-Scan) and a reference (gold standard) PCI optical biometer (IOLMaster 500). SETTING: Service d'Ophtalmologie, Hopital Bicêtre, APHP Université, Paris, France. DESIGN: Evaluation of a diagnostic device. METHODS: One eye of consecutive patients scheduled for cataract surgery was measured. Biometry was performed with the new biometer and the reference biometer. Comparisons were performed for AL, average K at 2.4 mm, ACD, IOL power calculations with the Haigis and SRK/T formulas, and postoperative predictability of the devices. A P value less than 0.05 was statistically significant. RESULTS: The study enrolled 50 patients (mean age 72.6 years±4.2 SEM). There was a good correlation between biometers for AL, K, and ACD measurements (r=0.999, r=0.933, and r=0.701, respectively) and between IOL power calculation with the Haigis formula (r=0.972) and the SRK/T formula (r=0.981). The mean absolute error (MAE) in IOL power prediction was 0.42±0.08 diopter (D) with the new biometer and 0.44±0.08 D with the reference biometer. The MAE was 0.20 D with the Haigis formula and 0.19 with the SRK/T formula (P=.36). CONCLUSION: The new PCI biometer provided valid measurements compared with the current gold standard, indicating that the new device can be used for IOL power calculations for routine cataract surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.